Mullerian inhibiting substance (MIS) is responsible for regression of Mullerian ducts during the course of male reproductive tract development and curiously, MIS is also expressed in both adult male testes and female ovaries, albeit at much lower levels. It is a TGF-beta family protein expressed in fetal Sertoli cells of the testis which transduces its signal into the cell via a heteromeric complex of type I and II receptors. The molecular mechanisms governing these processes are largely unknown as is the role played by MIS in the adult. Our primary goal is to identify and characterized the MIS receptor components in order to delineate the molecular details of MIS-mediated regression of Mullerian ducts and to determine the roles played by MIS in the adult. We have cloned putative MIS type I and type II receptors in the laboratory, R1 and pBS7, respectively, which are expressed in the appropriate tissues in a temporal manner. The type I receptor is being studied by others in the laboratory, whereas the molecular characterization of the MIS type II receptor (pBS7), is the focus of this proposal. We will confirm by qualitative and quantitative techniques that pBS7 is the MIS type II receptor. We will perform gene disruption in mice to determine the phenotype of type II receptor knockout. Finally, we will study the 5' flanking region of the type II receptor in order to better understand the molecular mechanism underlying its transcriptional regulation. The results of these efforts will allow us to understand the roles played by MIS in fetal development and in the adult.